Abstract
IntroductionExtensive mammographic density in women is associated with increased risk for breast cancer. Mouse models provide a powerful approach to the study of human diseases, but there is currently no model that is suited to the study of mammographic density.MethodsWe performed individual manipulations of the stromal, epithelial and matrix components of the mouse mammary gland and examined the alterations using in vivo and ex vivo radiology, whole mount staining and histology.ResultsAreas of density were generated that resembled densities in mammographic images of the human breast, and the nature of the imposed changes was confirmed at the cellular level. Furthermore, two genetic models, one deficient in epithelial structure (Pten conditional tissue specific knockout) and one with hyperplastic epithelium and mammary tumors (MMTV-PyMT), were used to examine radiographic density.ConclusionOur data show the feasibility of altering and imaging mouse mammary gland radiographic density by experimental and genetic means, providing the first step toward modelling the biological processes that are responsible for mammographic density in the mouse.
Highlights
Extensive mammographic density in women is associated with increased risk for breast cancer
Areas of density were generated that resembled densities in mammographic images of the human breast, and the Conclusion Our data show the feasibility of altering and imaging mouse mammary gland radiographic density by experimental and genetic means, providing the first step toward modelling the biological processes that are responsible for mammographic density in the mouse
Having found that expanded epithelial structures formed during gestation correlated with increased mammographic density, we examined whether mammary gland with hypoplastic epithelium would exhibit reduced radiographic density
Summary
Extensive mammographic density in women is associated with increased risk for breast cancer. Mouse models provide a powerful approach to the study of human diseases, but there is currently no model that is suited to the study of mammographic density. Women with mammographic density in more than 75% of breast tissue are at four to six times higher risk for developing breast cancer than those with little or no density [5,10,14]. Disease modelling in mice has become a powerful tool for investigating the physiological and genetic factors that are involved in human disease. It is not known whether mammary gland density is a risk factor in mice because a suitable mouse model in which to study mammary density is currently lacking.
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